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FLASH GENE
Symbol CDH5 contributors: mct - updated : 11-07-2019
HGNC name cadherin 5, type 2, VE-cadherin (vascular epithelium)
HGNC id 1764
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N terminal hydrophobic domain
  • five extracellular cadherin repeats with four cysteines in the most proximal (MPED)
  • a transmembrane segment and a highly conserved cytoplasmic tail required for interactions
    • conjugated GlycoP
    HOMOLOGY
    Homologene
    FAMILY cadherin superfamily of calcium dependent cell-cell adhesion glycoproteins
    CATEGORY adhesion
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,tight
    basic FUNCTION
  • transmembrane glycoprotein component of adherens junction
  • involved in cell-cell or cell-ECM interactions
  • having a function in tumor progression
  • mediates contact inhibition of cell growth in quiescent endothelial cell layers
  • playing a role in modulating c-Src activation in VEGF signaling, thus providing new insights into the importance of CDH5 in VEGF signaling and vascular function
  • positive and endothelial cells -specific regulator of TGF-beta signaling
  • required for efficient ALK-dependent Smad phosphorylation as shown by faster and more potent activation of Smad1/5 and SMAD2/3 signaling
  • endothelial specific cell-cell adhesion molecule, plays a pivotal role in the formation, maturation and remodeling of the vascular wall
  • antagonizes VEGFR2 signaling, and consequently, inhibition of CDH5, Rho-kinase, or actomyosin contractility leads to VEGF-driven, RAC1-dependent sprouting
  • CDH5 and PECAM1 enhance acute lymphoblastic leukemia migration across brain microvascular endothelial cell monolayers
  • plasticity of the CDH5-CTNNA1 complex is central for the leukocyte diapedesis mechanism
  • controls potentially vascular permeability and limits fibrogenesis after Unilateral ureteral obstruction
  • vinculin-dependent cadherin mechanosensing in endothelial processes such as leukocyte extravasation and angiogenesis
  • CDH5-homophilic adhesion controls endothelial barrier permeability through assembly of adherens junctions (AJs)
  • major adherens junction adhesion molecule in endothelial cells
  • CDH5, NECTIN2, and CLDN5 are involved in the regulation of vascular permeability in a mutually interacting manner, which indicates their prominent role for the functionality of the human corpus luteum
  • its phosphorylation and binding partner status are important indicators of endothelial permeability
  • CDH5 organizes junctional and cortical actin cytoskeletons
  • chiefly organizes the opening and closing of the endothelial barrier, and is central in permeability changes
  • RNA-binding protein quaking maintains endothelial barrier function and affects CDH5 and CTNNB1 protein expression
  • novel junction protective mechanism during polarized trafficking of CDH5, which supports barrier maintenance within dynamic endothelial tissue
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • AMOTL2/CDH5 complex is responsible for transmitting mechanical force between endothelial cells for the coordination of cellular morphogenesis consistent with aortic lumen expansion and function
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • hemophilic, calcium dependent interactions
  • interacting by its C terminus with the cytoskeleton via beta-catenin
  • interacting with CSK (CSK binds via its SH2 domain to the phosphorylated tyrosine 685 of CDH5)
  • directly or indirectly associates with many other signaling molecules, including vascular endothelial cell growth factor receptor 2 (KDR)
  • interacting with KLF4 (key role of KLF4 in the regulation of CDH5 expression at the level of the adherens junctions and in the acquisition of CDH5-mediated endothelial barrier function)
  • PECAM1 is associated with CDH5 and may similarly regulate its signaling via recruitment of PTPN6/PTPN11
  • interacting with JCAD (JCAD is not essential for CDH5-mediated cell–cell adhesion)
  • SOX7 binds and activates the promoter of CDH5, demonstrating that this gene is a novel downstream transcriptional target of SOX7
  • PTPN11 controls the recovery of endothelial barrier function by dephosphorylating CTNNB1 and promoting the mobility of CDH5 at the plasma membrane
  • CDH5-mediated adhesion modulates steady-state microtubules (MT) dynamics by suppressing MT growth
  • CDH5 outside-in signaling regulates cytosolic Ca2+ homeostasis and MAPRE3 phosphorylation, which are required for assembly of adherens junctions (AJs)
  • CHRM3 facilitates interaction of the CDH5-based adherens junctional complex and the actin-based cytoskeleton by maintaining RAC1 activity, which regulates the interaction between IQGAP1/RAC1 and IQGAP1/CTNNB1, and may contribute to endothelial barrier function under physiological conditions
  • AMOTL2 associates to the CDH5 adhesion complex where it couples adherens junctions to contractile actin fibres
  • interacts with CTNND1and CTNNB1 through its cytoplasmic tail
  • regulates transendothelial permeability in synergy with RRAS and CDH5 in an endothelial monolayer
  • importance of spatio-temporal regulation of the actin cytoskeleton through TRIO and RAC1 at CDH5-based cell-cell junctions in the maintenance of the endothelial barrier
  • EPS8, a signaling adapter regulating actin dynamics, is a novel partner of CDH5 and is able to modulate YAP1 activity 7)
  • new role for PACSIN2 in the control of CDH5-based endothelial adhesion
  • biological activity of CDH5 in regulating endothelial polarity and vascular lumen formation is mediated through its interaction with the two cell polarity proteins PALS1 and PARD3
  • CMTM3 is involved in CDH5 turnover and is a regulator of the cell surface pool of CDH5
  • endothelial TSPAN5- and TSPAN17-ADAM10 complexes may regulate inflammation by maintaining normal CDH5 expression and promoting T lymphocyte transmigration
  • endothelial cell PTPN11 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM1-CDH5 interaction
  • endothelial flow mechanotransduction through the junctional complex is mediated by a specific pool of CDH5 that is phosphorylated on Y658 and bound to GPSM2
  • CGNL1 regulates vascular growth by promoting CDH5 association with the actin cytoskeleton, thereby stabilizing adherens junctions
  • functional interaction of CDH5 with the cell polarity protein PALS1
    • cell & other
    REGULATION
    Other phosphorylation of CDH5 controls endothelial phenotypes via CTNND1 coupling and RAC1 activation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    aberrantly expressed in invasive breast carcinomas
    constitutional     --over  
    in late onset preeclampsia significantly more expressed compared to late controls (differential expression of CDH5 and VEGFR2 in placental syncytiotrophoblast during preeclampsia)
    constitutional     --over  
    of circulating CDH5 and FABP1 in association with drug-induced liver injury
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS